An evidence-based oral hygiene education program for nursing staff.

Increasing evidence shows strong statistical correlations between improved oral hygiene and reduction in the incidence, and mortality, from health care-associated pneumonia among elderly. Therefore, it is important that nursing staff are well educated in oral hygiene. The objective was to describe the design of a new oral hygiene educational program for nursing staff, where the theoretical parts of the education were integrated with evidence about the preventive effect of improved oral care on respiratory tract infections and health care-associated pneumonia among hospitalized or nursing home resident older people. An educational model was translated into three educational steps: hands-on training, group discussions, and a theoretical lecture including scientific evidence about the preventive effect of oral hygiene on respiratory tract infections, and health care-associated pneumonia, among older people. Evidence-based oral hygiene education seems to be a feasible way to increase the motivation for daily oral care tasks among nursing staff, and thus to improve the oral hygiene status among the nursing home resident elderly. Further studies are, however, needed to further evaluate the effect of evidence-based oral hygiene educations in different health care settings and over longer time periods.

A survey of attitudes and perceptions toward oral hygiene among staff at a geriatric nursing home.

The aim of this survey was to test the impact of an oral hygiene educational model on attitudes and perceptions toward oral hygiene among nursing home staff members. A pilot questionnaire was distributed to the nursing staff before and after a course on oral hygiene at a geriatric nursing home in Stockholm in 2008. The nursing staff was of the opinion that they had sufficient time to carry out oral hygiene tasks but considered such tasks unpleasant, mainly because of unwillingness and resistance from the residents. These attitudes and perceptions among the nursing staff did not change significantly after oral hygiene education. Future oral hygiene educational models need to be developed with an aim to alter the perceptions and behavior of the nursing home staff.

Dental hygiene education for nursing staff in a nursing home for older people.

AIM: This paper is a report of a study evaluating the effect of a repeated education programme for nursing staff in a home for older people. BACKGROUND: A strong relationship exists between oral infections and general health complications (especially aspiration pneumonia) among nursing home residents and hospitalized older people. Thus, nursing staff need to be educated in oral hygiene measures. METHODS: Forty-three nursing home resident older people (12 men, 31 women, age range 69-99 years) were included in a dental hygiene and gingivitis evaluation using gingival bleeding scores and modified plaque scores. Evaluation was conducted before and 3 weeks after a repeated dental hygiene education for nursing staff at a nursing home in Sweden in 2008. Dental hygiene education had been given 1.5 years previously. FINDINGS: Forty-one residents (12 men and 29 women) were available for evaluation after the repeated dental hygiene education (one died, one had had teeth extracted). There was a reduction in gingival bleeding scores (P < 0.001), and in plaque scores (P < 0.001). CONCLUSION: Repeated dental hygiene education improves the dental hygiene among nursing home resident older people. In order to succeed it may be necessary to address attitudes and perceptions towards oral care in such a dental hygiene education programme for nursing staff. Improved oral hygiene contributes to reducing the incidence of healthcare-associated pneumonia among nursing home resident older people, and thus to reduced healthcare costs.

Evaluation of dental hygiene education for nursing home staff.

AIM: This paper is a report of a study evaluating the long-term effects on the oral hygiene status of older nursing home residents one and a half years after dental hygiene education was given to the staff. BACKGROUND: A strong relationship exists between oral infections and general health complications (especially aspiration pneumonia) among nursing home residents and hospitalized older people. It is therefore important to educate nursing home staff in oral hygiene measures and to follow up the effects of the education over time. METHODS: Dental plaque measurements were conducted at a Swedish nursing home in 2006-2008. Forty-one residents (12 men, 31 women, aged 69-99 years) fulfilled the inclusion criteria and participated in a dental hygiene evaluation 1.5 years after dental hygiene education was given to the staff at the nursing home. Plaque index scores (year 2008) were compared to those soon after the education (year 2006). FINDINGS: After the dental hygiene education in 2006, 60 nursing home residents (14 men, 46 women) were available for plaque index measurements, whereas 41 residents (12 men, 29 women) were available 1.5 years later. The median plaque index scores were 17.0 (n = 60) in 2006, and 18.0 (n = 41) in 2008 (Mann-Whitney U-test, P > 0.05). CONCLUSION: Dental hygiene education for nursing home staff is important to maintain an adequate level of oral hygiene among older nursing home residents over time. Follow-up of dental hygiene education for nursing home staff is recommended to maintain a sufficient level of oral hygiene among the residents.

Dental hygiene education for nursing staff.

The aim of this study was to describe a new dental hygiene education program for nursing staff and to report experiences from the program at a nursing home in Stockholm, Sweden (2006). This strategy comprises 3 steps. The first is individual instruction for nursing staff about oral care for patients and hands-on training in toothbrushing technique using an electric toothbrush. The second step was small discussion groups of 4 to 8 nursing staff, led by a dental hygienist and a psychologist. The third step was a theoretical lecture focusing on the associations among dental hygiene, oral health, and general health among the elderly. During the dental hygiene education program, a negative attitude toward oral care was noted among members of the nursing staff, although they did consider oral care important for their patients. Increased self-confidence of staff in providing oral care was noted after completing the dental hygiene education program. Nursing staff members stated that they had received more detailed knowledge about oral care during the program. This dental hygiene education program appears to result in increased knowledge and interest in oral hygiene tasks among the nursing staff and may lead to improved dental hygiene among nursing home residents.

Convection-enhanced delivery of nanoliposomal CPT-11 (irinotecan) and PEGylated liposomal doxorubicin (Doxil) in rodent intracranial brain tumor xenografts.

We have previously shown that convection-enhanced delivery (CED) of highly stable nanoparticle/liposome agents encapsulating chemotherapeutic drugs is effective against intracranial rodent brain tumor xenografts. In this study, we have evaluated the combination of a newly developed nanoparticle/liposome containing the topoisomerase I inhibitor CPT-11 (nanoliposomal CPT-11 [nLs-CPT-11]), and PEGylated liposomal doxorubicin (Doxil) containing the topoisomerase II inhibitor doxorubicin. Both drugs were detectable in the CNS for more than 36 days after a single CED application. Tissue half-life was 16.7 days for nLs-CPT-11 and 10.9 days for Doxil. The combination of the two agents produced synergistic cytotoxicity in vitro. In vivo in U251MG and U87MG intracranial rodent xenograft models, CED of the combination was also more efficacious than either agent used singly. Analysis of the parameters involved in this approach indicated that tissue pharmacokinetics, tumor microanatomy, and biochemical interactions of the drugs all contributed to the therapeutic efficacy observed. These findings have implications for further clinical applications of CED-based treatment of brain tumors.

Anxiogenic and aversive effects of corticotropin-releasing factor (CRF) in the bed nucleus of the stria terminalis in the rat: role of CRF receptor subtypes.

RATIONALE: Corticotropin-releasing factor (CRF) produces anxiety-like and aversive effects when infused directly into the various regions of the brain, including the bed nucleus of the stria terminalis (BNST). However, the CRF receptor subtypes within the BNST mediating these phenomena have not been established. OBJECTIVES: We used selective CRF receptor antagonists to determine the receptor subtypes involved in the anxiogenic-like and aversive effects CRF in the BNST. MATERIALS AND METHODS: Male Long-Evans rats were bilaterally infused with CRF (0.2 or 1.0 nmol) either alone or in combination with the CRF1 receptor antagonist CP154,526 or the CRF2 receptor antagonist anti-sauvagine 30 (AS30) before behavioral testing in the elevated plus maze or place conditioning paradigms. RESULTS: Intra-BNST administration of CRF produced a dose-dependent reduction in open arm entries and open arm time in the elevated plus maze, indicating an anxiogenic-like effect. These effects were inhibited by co-infusion of CP154,526 but not of AS30, indicating that the anxiogenic-like effects of CRF in the BNST are mediated by CRF1 receptors. Place conditioning with intra-BNST administration of CRF produced a dose-dependent aversion to the CRF-paired environment that was prevented by co-infusion of either CP154,526 or AS30, indicating that both CRF receptor subtypes mediate the aversive effects of this peptide. Intra-BNST infusions of the CRF receptor antagonists alone produced no effects in either behavioral paradigm. CONCLUSIONS: CRF1 receptors in the BNST mediate the anxiogenic-like effects of CRF in this region, whereas both CRF1 and CRF2 receptor subtypes mediate the conditioned aversive effects of this peptide within the BNST.

EGF-receptor targeted liposomes with boronated acridine: growth inhibition of cultured glioma cells after neutron irradiation.

PURPOSE: To study survival of cultured U-343MGaCl 2:6 glioma cells after incubation with boron-containing liposomes targeting the epidermal growth factor receptor following neutron irradiation. MATERIALS AND METHODS: Epidermal growth factor-tagged liposomes were loaded with water-soluble boronated acridine developed for boron neutron capture therapy, (BNCT). Cellular uptake and distribution were studied. Further, cells were placed at 3 cm depth in a phantom and exposed to an epithermal neutron beam to study clonogenic cell survival. RESULTS: The cellular uptake of boron reached 90 ppm and it was determined by subcellular fractionation that most of the cell-associated boron was located outside of the nucleus. For clonogenic survival, the cells were incubated with epidermal growth factor receptor-targeted liposomes for 4 hours resulting in a cellular concentration of 55 ppm boron (11 ppm 10B). At a fluence of 3 x 10(12) neutrons/cm2 the cell killing effect of the boron-containing epidermal growth factor-liposomes was about ten times higher than for neutrons only. Furthermore, theoretical calculation of the survival by enriched compound (55 ppm 10B), using the parameters from non-enriched compound (11 ppm 10B), shows that the killing effect in this case would be approximately five orders of magnitude higher than for neutrons only. CONCLUSION: The results in this study show that epidermal growth factor-receptor targeted liposomes are suitable as tumor-cell delivery agents of boron for BNCT and support further studies to demonstrate their effectiveness in vivo.

An aminoacridine derivative for radionuclide therapy: DNA binding properties studied in a novel cell-free in vitro assay.

Radiolabelled DNA-binding compounds can be used to increase the efficiency of radionuclide cancer therapy of disseminated disease. In this work, the aminoacridine compound N-[3-(acridine-9-ylamino)-propyl]-3-iodobenzamide (A3) labelled with the Auger-emitting nuclide 125I using Chloramine-T was studied. Optimal labelling conditions of 125I-A3 were investigated and the interaction with DNA was studied using a novel cell-free in vitro assay with naked human genomic DNA in agarose plugs. This novel assay showed to be simple and reliable. The results verify that 125I-A3 specifically binds DNA with low dissociation and is potent in causing double-strand breaks, yielding 1.0-1.4 breaks per decay. In conclusion, 125I-A3 is a most suitable DNA-binding compound for future therapeutic studies of Auger-electron emitters like 125I.

Trastuzumab-conjugated boron-containing liposomes for tumor-cell targeting; development and cellular studies.

The goal of the present study was to investigate HER-2-targeted boron-containing liposomes as a potential drug delivery vehicle for boron neutron capture therapy (BNCT). Trastuzumab was conjugated to the distal end of PEG-DSPE-NHS in micelles and the Trastuzumab-PEG-DSPE were then transferred to preformed liposomes, either empty or loaded with water soluble boronated acridine (WSA), using the micelle transfer method. The final conjugates were referred to as Trastuzumab-liposome and Trastuzumab-liposome-WSA. The binding specificity, uptake, retention and internalization of Trastuzumab-liposome-WSA conjugates were studied in cultured SK-BR-3 cells, with regard to the targeting agent, carrier, and the load. The subcellular location of WSA was studied using confocal microscopy. The conjugates showed specific binding to the HER-2 receptors of SK-BR-3 cells. High cellular uptake and internalization of the conjugates was seen, reaching 132 ppm of boron in the targeted cells after 24 h. WSA was distributed mainly in the cytoplasm and was shown to have long cellular retention, with 90% and 67% of the boron remained in the cells after 24 h and 48 h, respectively. The conjugate Trastuzumab-liposome-WSA could be considered as a potent drug delivery system for BNCT.

Introductory experiments on ligand liposomes as delivery agents for boron neutron capture therapy.

Liposomes are, when coupled to receptor ligands, candidates for receptor mediated delivery of boron for tumour therapy since they have capacity to deliver large amounts of boron per receptor interaction. With EGF-liposomes we present a pegylated ligand liposome delivery vehicle, containing water soluble boronated phenanthridine, WSP1, or water soluble boronated acridine, WSA1, for EGFR targeting. In the case of WSA1 a ligand dependent uptake was obtained and the boron uptake was as good as if free WSA1 was given. No ligand dependent boron uptake was seen for WSP1 containing liposomes. Thus, WSA1 is a candidate for further studies. Approximately 10(5) boron atoms were in each liposome. A critical assessment indicates that after optimization up to 10(6) boron atoms can be loaded. Since it is known that, for therapeutic effect, approximately 10(8)-10(9) boron atoms are needed in a single tumour cell it is realized that 10(2)-10(3) receptor interactions are needed to meet the demand. Tests applying cultured glioma cells indicate, without optimization of the delivery conditions, a boron uptake in the ppm range, which is necessary for successful BNCT. Thus, it seems possible to kill micro-invasive tumour cells with targeted liposomes if the delivery conditions are optimal.

Ligand liposomes and boron neutron capture therapy.

Boron neutron capture therapy (BNCT) has been used both experimentally and clinically for the treatment of gliomas and melanomas, with varying results. However, the therapeutic effects on micro-invasive tumor cells are not clear. The two drugs that have been used clinically, p-boronophenylalanine, (BPA), and the sulfhydryl borane, (BSH), seem to be taken up preferentially in solid tumor areas but it is uncertain whether enough boron is taken up by micro-invasive tumor cells. To increase the selective uptake of boron by such cells, would be to exploit tumor transformation related cellular changes such as over-expression of growth factor receptors. However, the number of receptors varies from small to large and the uptake of large amounts of boron for each receptor interaction is necessary in order to deliver sufficient amounts of boron. Therefore, each targeting moiety must deliver large number of boron atoms. One possible way to meet these requirements would be to use receptor-targeting ligand liposomes, containing large number of boron atoms. This will be the subject of this review and studies of boron containing liposomes, with or without ligand, will be discussed. Two recent examples from the literature are ligand liposomes targeting either folate or epidermal growth factor (EGF) receptors on tumor cells. Other potential receptors on gliomas include PDGFR and EGFRvIII. Besides the appropriate choice of target receptor, it is also important to consider delivery of the ligand liposomes, their pharmacodynamics and pharmacokinetics and cellular processing, subjects that also will be discussed in this review.

Tumor-cell targeted epiderimal growth factor liposomes loaded with boronated acridine: uptake and processing.

PURPOSE: The aim of this work was to investigate the cellular binding and processing of polyethylene glycol-stabilized epidermal growth factor (EGF) liposomes. The liposomes were actively loaded with water-soluble boronated acridine (WSA), primarily developed for boron neutron capture therapy. METHODS: The uptake, internalization, and retention of EGF-liposome conjugates were studied in two cultured monolayer cell-lines, A-431 and U-343, with regard to the nuclide-label on the targeting agent, the carrier, and the load. The subcellular localization of WSA was studied using confocal microscopy. RESULTS: We found that the liposome complex was internalized after specific binding to the EGF receptor. After internalization in the tumor cells, WSA was distributed mainly in the cytoplasm and was shown to have long cellular retention, with 80% of the boron remaining after 48 h. CONCLUSIONS: The long retention of the compound and the cellular boron concentration reached makes these targeted liposomes interesting for further development toward boron neutron capture therapy.

Development of EGF-conjugated liposomes for targeted delivery of boronated DNA-binding agents.

Liposomes are of interest as drug delivery tools for therapy of cancer and infectious diseases. We investigated conjugation of epidermal growth factor, EGF, to liposomes using the micelle-transfer method. EGF was conjugated to the distal end of PEG-DSPE lipid molecules in a micellar solution and the EGF-PEG-DSPE lipids were then transferred to preformed liposomes, either empty or containing the DNA-binding compound, water soluble acridine, WSA. We found that the optimal transfer conditions were a 1-h incubation at 60 degrees C. The final conjugate, (125)I-EGF-liposome-WSA, contained approximately 5 mol % PEG, 10-15 EGF molecules at the liposome surface, and 10(4) to 10(5) encapsulated WSA molecules could be loaded. The conjugate was shown to have EGF-receptor-specific cellular binding in cultured human glioma cells.